Live attenuated SARS-CoV-2 vaccine candidate: Protective immunity without serious lung lesions in Syrian hamsters

Various COVID-19 vaccine candidates are currently under clinical trial. However, no live attenuated vaccine has been developed yet, despite their generally high efficacy. Here, we established temperature-sensitive mutant strains of SARS-CoV-2, whose growth was significantly slower than that of the parent strain at 37{degrees}C. One of the strains, A50-18, which presented mutations in nonstructural protein 14, did not replicate at all at 37{degrees}C in vitro. In vivo experiments demonstrated that this strain replicated inefficiently in the lungs of Syrian hamsters, and intra-nasal inoculation induced sufficient anti-SARS-CoV-2-neutralizing antibodies to protect against wild type virus infection. These results suggest that the A50-18 strain could be a promising live attenuated vaccine candidate against SARS-CoV-2. One Sentence SummaryA live attenuated virus provided immunity against SARS-CoV-2 in an animal model, making it a promising vaccine candidate.